ZMIZ1zinc finger MIZ-type containing 1
Autism Reports / Total Reports
7 / 12Rare Variants / Common Variants
25 / 0Aliases
ZMIZ1, MIZ, NEDDFSA, RAI17, TRAFIP10, ZIMP10Associated Syndromes
-Chromosome Band
10q22.3Associated Disorders
ADHD, ASDRelevance to Autism
Analysis of whole-genome sequencing data in Liu et al., 2018 demonstrated that a distal enhancer putatively targeting the ZMIZ1 gene harbored recurrent de novo single-nucleotide variants in ASD-affected cases. Carapito et al., 2019 reported 19 individuals with ZMIZ1 variants presenting with a neurodevelopmental syndrome characterized by developmental delay/intellectual disability, growth failure, feeding difficulties, microcephaly, facial dysmorphism, and various other congenital malformations; behavioral abnormalities, including autism spectrum disorder, were frequently observed in affected individuals.
Molecular Function
This gene encodes a member of the PIAS (protein inhibitor of activated STAT) family of proteins. The encoded protein regulates the activity of various transcription factors, including the androgen receptor, Smad3/4, and p53. The encoded protein may also play a role in sumoylation.
External Links
SFARI Genomic Platforms
Reports related to ZMIZ1 (12 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Support | A de novo t(10;19)(q22.3;q13.33) leads to ZMIZ1/PRR12 reciprocal fusion transcripts in a girl with intellectual disability and neuropsychiatric alterations | Crdova-Fletes C , et al. (2015) | No | Behavioral abnormalities |
| 2 | Primary | A Statistical Framework for Mapping Risk Genes from De Novo Mutations in Whole-Genome-Sequencing Studies | Liu Y , et al. (2018) | Yes | - |
| 3 | Recent recommendation | ZMIZ1 Variants Cause a Syndromic Neurodevelopmental Disorder | Carapito R , et al. (2019) | No | ASD |
| 4 | Support | Autosomal dominant inheritance in a recently described ZMIZ1-related neurodevelopmental disorder: Case report of siblings and an affected parent | Latchman K , et al. (2019) | No | ADHD, autistic features |
| 5 | Support | - | Mahjani B et al. (2021) | Yes | - |
| 6 | Support | - | Woodbury-Smith M et al. (2022) | Yes | - |
| 7 | Support | - | Brea-Fernández AJ et al. (2022) | No | - |
| 8 | Support | - | Zhou X et al. (2022) | Yes | - |
| 9 | Support | - | Bartolomaeus T et al. (2023) | No | - |
| 10 | Support | - | Sheth F et al. (2023) | Yes | DD, ID |
| 11 | Support | - | Amerh S Alqahtani et al. (2023) | Yes | - |
| 12 | Support | - | Rajan K C et al. (2024) | Yes | - |
Rare Variants (25)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | translocation | De novo | - | Simplex | 30639322 | Carapito R , et al. (2019) | |
| - | - | translocation | De novo | - | Simplex | 26163108 | Crdova-Fletes C , et al. (2015) | |
| c.1744A>G | p.Asn582Asp | missense_variant | Unknown | - | - | 34615535 | Mahjani B et al. (2021) | |
| c.10A>G | p.Met4Val | missense_variant | De novo | - | Multiplex | 35982159 | Zhou X et al. (2022) | |
| c.3097-2A>G | - | splice_site_variant | De novo | - | Simplex | 30639322 | Carapito R , et al. (2019) | |
| c.2323G>A | p.Glu775Lys | missense_variant | Unknown | - | Simplex | 37543562 | Sheth F et al. (2023) | |
| c.2607G>A | p.Pro869%3D | synonymous_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.272A>G | p.Lys91Arg | missense_variant | De novo | - | Simplex | 30639322 | Carapito R , et al. (2019) | |
| c.2456C>T | p.Thr819Met | missense_variant | Unknown | - | - | 35205252 | Woodbury-Smith M et al. (2022) | |
| c.2835+4A>T | - | splice_region_variant | De novo | - | - | 35322241 | Brea-Fernández AJ et al. (2022) | |
| c.859G>A | p.Ala287Thr | missense_variant | De novo | - | Simplex | 30639322 | Carapito R , et al. (2019) | |
| c.887C>A | p.Thr296Lys | missense_variant | De novo | - | Simplex | 30639322 | Carapito R , et al. (2019) | |
| c.887C>T | p.Thr296Ile | missense_variant | De novo | - | Simplex | 30639322 | Carapito R , et al. (2019) | |
| c.893C>T | p.Thr298Ile | missense_variant | De novo | - | Simplex | 30639322 | Carapito R , et al. (2019) | |
| c.899C>T | p.Thr300Met | missense_variant | De novo | - | Simplex | 30639322 | Carapito R , et al. (2019) | |
| c.2610C>T | p.Ser870= | synonymous_variant | De novo | - | Simplex | 30639322 | Carapito R , et al. (2019) | |
| c.328C>T | p.Arg110Ter | stop_gained | Unknown | - | Multiplex | 37799141 | Amerh S Alqahtani et al. (2023) | |
| c.418T>C | p.Ser140Pro | missense_variant | Unknown | - | Multiplex | 37460657 | Bartolomaeus T et al. (2023) | |
| c.1386dup | p.Thr463HisfsTer14 | frameshift_variant | De novo | - | Simplex | 30639322 | Carapito R , et al. (2019) | |
| c.2758dup | p.Gln920ProfsTer34 | frameshift_variant | De novo | - | Simplex | 30639322 | Carapito R , et al. (2019) | |
| c.2835del | p.Met946CysfsTer61 | frameshift_variant | De novo | - | Simplex | 30639322 | Carapito R , et al. (2019) | |
| c.3021del | p.Phe1008LeufsTer7 | frameshift_variant | De novo | - | Simplex | 30639322 | Carapito R , et al. (2019) | |
| c.3112dup | p.Thr1038AsnfsTer4 | frameshift_variant | De novo | - | Simplex | 30639322 | Carapito R , et al. (2019) | |
| c.1386dup | p.Thr463HisfsTer14 | frameshift_variant | Unknown | - | Multiplex | 30639322 | Carapito R , et al. (2019) | |
| c.1310del | p.Pro437ArgfsTer84 | frameshift_variant | Familial | Paternal | Multiplex | 31833199 | Latchman K , et al. (2019) |
Common Variants
No common variants reported.
SFARI Gene score
2S
Strong Candidate, Syndromic
Score Delta: Score remained at 2S
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
4/1/2022
2S
Increased from to 2S
Krishnan Probability Score
Score 0.52341583538816
Ranking 1650/25841 scored genes
[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning
approach on a human brain-specific gene network. The method was first presented in Nat
Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed
in column G of supplementary table 3 (see:
http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser,
with the ability to view networks of associated ASD risk genes, can be found at
asd.princeton.edu.
ExAC Score
Score 0.9997437008725
Ranking 812/18225 scored genes
[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has
been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by
Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at
exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of-
function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of-
function mutations in autism in such a gene would be more likely to confer risk. For a full list of
pLI scores see:
ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle
aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score
Score 0.94627625165325
Ranking 16805/18665 scored genes
[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013),
and is a statistic that integrates evidence from both de novo and transmitted mutations.
It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233
(2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper
(the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Zhang D Score
Score 0.41481032923338
Ranking 1290/20870 scored genes
[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures),
or D score, was developed to combine evidence from de novo loss-of- function mutation with
evidence from cell-type- specific gene expression in the mouse brain (specifically translational
profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with
positive D scores are more likely to be associated with autism risk, with higher-confidence genes
having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204-
215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in
supplementary table 2 from that paper.